Povidone-iodine (PVP-I) is a time-tested antiseptic agent with excellent virucidal (99.99%) properties. Repurposing it against coronavirus disease-19 (COVID-19) is a relatively newer concept and has been sparsely tested in vivo. The most common route of entry of severe acute respiratory syndrome coronavirus 2 (SARS CoV-2) is the nasopharynx. Averting colonization of the virus could be one of the best options to reduce the incidence of infection. PVP-I gargle and mouthwash were found to be effective in vitro rapid inactivation against SARS-CoV-2 on a smaller scale (Hassandarvish et al. in BDJ 1-4, 2020, Pelletier et al. in ENTJ 1-5, 2020). However, efficacy in humans is lacking. To assess the virucidal effect of PVP-I against SARS-CoV-2 located in the nasopharynx was the objective of this parallel armed randomized clinical trial. We screened all RT-PCR-confirmed COVID-19 cases aged 18 years and above with symptoms. Written informed consent was obtained before randomization. Nasopharyngeal clearance of SARS-CoV-2 was tested after single time application of PVP-I nasal irrigation (NI) at diluted concentrations of .4%, .5% and .6% and PVP-I nasal spray (NS) at diluted concentrations of .5% and .6%. All groups were compared to the corresponding controls (distilled water). The primary outcome was viral clearance in a repeat RT-PCR (qualitative), and the secondary outcome was the number of adverse events. Final data analysis was performed using the statistical software SPSS (Version 20). A total of 189 confirmed COVID-19 cases were randomized into seven groups: 27 patients in each group. Of all, 159 (84.1%) were male, and 30 (15.9%) were female. We observed a statistically significant proportion of nasopharyngeal clearance with all strengths of PVP-I NI and PVP-I NS compared to the corresponding controls. Additionally, 0.5% NI was significantly better than 0.5% NS for viral clearance (p = 0.018) and had the highest nasopharyngeal clearance among all & Mostafa Kamal Arefin